IREB2 and GALC are associated with pulmonary artery enlargement in chronic obstructive pulmonary disease.

Jin Hwa Lee; J Michael Wells; James D Crapo; Elizabeth A Regan; Stephanie Bratschie; Rochelle Lantz; Sandra Melanson; Lori Stepp; Terri Beaty; Douglas Everett; David Lynch; E Rand Sutherland; Eugene R Bleecker; Ronald G Crystal; James C Hogg; Michael A Province; Duncan C Thomas; Thomas Croxton; Weiniu Gan; Lisa Postow; John W Walsh; Delia Prieto; Homayoon Farzadegan; Samantha Bragan; Stacey Cayetano; Daniel Cossette; Roxanne K Kelly; Andre Williams; Ruthie Knowles; Carla Wilson; John Hokanson; Jennifer Black-Shinn; Gregory Kinney; Peter J Castaldi; Michael Cho; Megan E Hardin; Craig Hersh; Jacqueline Hetmanski; Nan Laird; Christoph Lange; Sharon M Lutz; Manuel Mattheisen; Merry-Lynn McDonald; Margaret M Parker; Stephanie Santorico; Emily S Wan; Jin Zhou; Mustafa Al Qaisi; Christian W Cox; Deanna Cusick; Jennifer G Dy; Shoshana Ginsburg; Eric A Hoffman; Philip F Judy; Alex Kluiber; Alexander McKenzie; John D Newell; John J Reilly; James Ross; Raul San Jose Estepar; Jered Sieren; Arkadiusz Sitek; Douglas Stinson; Alejandro Cornellas; Fernando Martinez; Robert Jensen; Jeffrey Curtis; Ella Kazerooni; M Philip Alapat; Venkata Bandi; Kalpalatha Guntupalli; Elizabeth Guy; Antara Mallampalli; Charles Trinh; Mustafa Atik; Hasan Al-Azzawi; Marc Willis; Susan Pinero; Linda Fahr; Arun Nachiappan; Collin Bray; L Alexander Frigini; Carlos Farinas; David Katz; Jose Freytes; AnneMarie Marciel; Dawn DeMeo; George Washko; Francine Jacobson; Hiroto Hatabu; Peter Clarke; Ritu Gill; Andetta Hunsaker; Beatrice Trotman-Dickenson; Rachna Madan; R Graham Barr; Byron Thomashow; John Austin; Belinda D'Souza; Neil MacIntyre; Richard Rosiello; Timothy Bresnahan; Joseph Bradley; Sharon Kuong; Steven Meller; Suzanne Roland; Charlene McEvoy; Joseph Tashjian; Robert Wise; Nadia Hansel; Robert Brown; Gregory Diette; Karen Horton; Janos Porszasz; Hans Fischer; Matt Budoff; Mehdi Rambod; Michael E DeBakey; Hirani Kamal; Roham Darvishi; Dennis Niewoehner; Quentin Anderson; Kathryn Rice; Audrey Caine; Marilyn Foreman; Gloria Westney; Eugene Berkowitz; Russell Bowler; Joyce Schroeder; Valerie Hale; John Armstrong; Debra Dyer; Jonathan Chung; Gerard Criner; Victor Kim; Nathaniel Marchetti; Aditi Satti; A James Mamary; Robert Steiner; Chandra Dass; Libby Cone; William Bailey; Mark Dransfield; Michael Wells; Surya Bhatt; Hrudaya Nath; Satinder Singh; Joe Ramsdell; Paul Friedman; Edwin van Beek; MeiLan Han; Christine Wendt; Tadashi Allen; Joel Weissfeld; Carl Fuhrman; Jessica Bon; Danielle Hooper; Sandra Adams; Carlos Orozco; Mario Ruiz; Amy Mumbower; Ariel Kruger; Carlos Restrepo; Michael Lane; Y Ivanov; K Kostov; J Bourbeau; M Fitzgerald; P Hernandez; K Killian; R Levy; F Maltais; D O'Donnell; J Krepelka; J Vestbo; E Wouters; D Quinn; P Bakke; M Kosnik; A Agusti; J Sauleda; P de Mallorca; Y Feschenko; V Gavrisyuk; L Yashina; N Monogarova; P Calverley; D Lomas; W MacNee; D Singh; J Wedzicha; A Anzueto; S Braman; R Casaburi; B Celli; G Giessel; M Gotfried; G Greenwald; N Hanania; D Mahler; B Make; S Rennard; C Rochester; P Scanlon; D Schuller; F Sciurba; A Sharafkhaneh; T Siler; E Silverman; R ZuWallack; H Coxson; C Crim; L Edwards; J Yates; B Miller; R Tal-Singer

doi:10.1165/rcmb.2014-0210OC

IREB2 and GALC are associated with pulmonary artery enlargement in chronic obstructive pulmonary disease.

Jin Hwa Lee, J Michael Wells, James D Crapo (Collaborator), Elizabeth A Regan (Collaborator), Stephanie Bratschie (Collaborator), Rochelle Lantz (Collaborator), Sandra Melanson (Collaborator), Lori Stepp (Collaborator), Terri Beaty (Collaborator), Douglas Everett (Collaborator), David Lynch (Collaborator), E Rand Sutherland (Collaborator), Eugene R Bleecker (Collaborator), Ronald G Crystal (Collaborator), James C Hogg (Collaborator), Michael A Province (Collaborator), Duncan C Thomas (Collaborator), Thomas Croxton (Collaborator), Weiniu Gan (Collaborator), Lisa Postow (Collaborator)John W Walsh (Collaborator), Delia Prieto (Collaborator), Homayoon Farzadegan (Collaborator), Samantha Bragan (Collaborator), Stacey Cayetano (Collaborator), Daniel Cossette (Collaborator), Roxanne K Kelly (Collaborator), Andre Williams (Collaborator), Ruthie Knowles (Collaborator), Carla Wilson (Collaborator), John Hokanson (Collaborator), Jennifer Black-Shinn (Collaborator), Gregory Kinney (Collaborator), Peter J Castaldi (Collaborator), Michael Cho (Collaborator), Megan E Hardin (Collaborator), Craig Hersh (Collaborator), Jacqueline Hetmanski (Collaborator), Nan Laird (Collaborator), Christoph Lange (Collaborator), Sharon M Lutz (Collaborator), Manuel Mattheisen (Collaborator), Merry-Lynn McDonald (Collaborator), Margaret M Parker (Collaborator), Stephanie Santorico (Collaborator), Emily S Wan (Collaborator), Jin Zhou (Collaborator), Mustafa Al Qaisi (Collaborator), Christian W Cox (Collaborator), Deanna Cusick (Collaborator), Jennifer G Dy (Collaborator), Shoshana Ginsburg (Collaborator), Eric A Hoffman (Collaborator), Philip F Judy (Collaborator), Alex Kluiber (Collaborator), Alexander McKenzie (Collaborator), John D Newell (Collaborator), John J Reilly (Collaborator), James Ross (Collaborator), Raul San Jose Estepar (Collaborator), Jered Sieren (Collaborator), Arkadiusz Sitek (Collaborator), Douglas Stinson (Collaborator), Alejandro Cornellas (Collaborator), Fernando Martinez (Collaborator), Robert Jensen (Collaborator), Jeffrey Curtis (Collaborator), Ella Kazerooni (Collaborator), M Philip Alapat (Collaborator), Venkata Bandi (Collaborator), Kalpalatha Guntupalli (Collaborator), Elizabeth Guy (Collaborator), Antara Mallampalli (Collaborator), Charles Trinh (Collaborator), Mustafa Atik (Collaborator), Hasan Al-Azzawi (Collaborator), Marc Willis (Collaborator), Susan Pinero (Collaborator), Linda Fahr (Collaborator), Arun Nachiappan (Collaborator), Collin Bray (Collaborator), L Alexander Frigini (Collaborator), Carlos Farinas (Collaborator), David Katz (Collaborator), Jose Freytes (Collaborator), AnneMarie Marciel (Collaborator), Dawn DeMeo (Collaborator), George Washko (Collaborator), Francine Jacobson (Collaborator), Hiroto Hatabu (Collaborator), Peter Clarke (Collaborator), Ritu Gill (Collaborator), Andetta Hunsaker (Collaborator), Beatrice Trotman-Dickenson (Collaborator), Rachna Madan (Collaborator), R Graham Barr (Collaborator), Byron Thomashow (Collaborator), John Austin (Collaborator), Belinda D'Souza (Collaborator), Neil MacIntyre (Collaborator), Richard Rosiello (Collaborator), Timothy Bresnahan (Collaborator), Joseph Bradley (Collaborator), Sharon Kuong (Collaborator), Steven Meller (Collaborator), Suzanne Roland (Collaborator), Charlene McEvoy (Collaborator), Joseph Tashjian (Collaborator), Robert Wise (Collaborator), Nadia Hansel (Collaborator), Robert Brown (Collaborator), Gregory Diette (Collaborator), Karen Horton (Collaborator), Janos Porszasz (Collaborator), Hans Fischer (Collaborator), Matt Budoff (Collaborator), Mehdi Rambod (Collaborator), Michael E DeBakey (Collaborator), Hirani Kamal (Collaborator), Roham Darvishi (Collaborator), Dennis Niewoehner (Collaborator), Quentin Anderson (Collaborator), Kathryn Rice (Collaborator), Audrey Caine (Collaborator), Marilyn Foreman (Collaborator), Gloria Westney (Collaborator), Eugene Berkowitz (Collaborator), Russell Bowler (Collaborator), Joyce Schroeder (Collaborator), Valerie Hale (Collaborator), John Armstrong (Collaborator), Debra Dyer (Collaborator), Jonathan Chung (Collaborator), Gerard Criner (Collaborator), Victor Kim (Collaborator), Nathaniel Marchetti (Collaborator), Aditi Satti (Collaborator), A James Mamary (Collaborator), Robert Steiner (Collaborator), Chandra Dass (Collaborator), Libby Cone (Collaborator), William Bailey (Collaborator), Mark Dransfield (Collaborator), Michael Wells (Collaborator), Surya Bhatt (Collaborator), Hrudaya Nath (Collaborator), Satinder Singh (Collaborator), Joe Ramsdell (Collaborator), Paul Friedman (Collaborator), Edwin van Beek (Collaborator), MeiLan Han (Collaborator), Christine Wendt (Collaborator), Tadashi Allen (Collaborator), Joel Weissfeld (Collaborator), Carl Fuhrman (Collaborator), Jessica Bon (Collaborator), Danielle Hooper (Collaborator), Sandra Adams (Collaborator), Carlos Orozco (Collaborator), Mario Ruiz (Collaborator), Amy Mumbower (Collaborator), Ariel Kruger (Collaborator), Carlos Restrepo (Collaborator), Michael Lane (Collaborator), Y Ivanov (Collaborator), K Kostov (Collaborator), J Bourbeau (Collaborator), M Fitzgerald (Collaborator), P Hernandez (Collaborator), K Killian (Collaborator), R Levy (Collaborator), F Maltais (Collaborator), D O'Donnell (Collaborator), J Krepelka (Collaborator), J Vestbo (Collaborator), E Wouters (Collaborator), D Quinn (Collaborator), P Bakke (Collaborator), M Kosnik (Collaborator), A Agusti (Collaborator), J Sauleda (Collaborator), P de Mallorca (Collaborator), Y Feschenko (Collaborator), V Gavrisyuk (Collaborator), L Yashina (Collaborator), N Monogarova (Collaborator), P Calverley (Collaborator), D Lomas (Collaborator), W MacNee (Collaborator), D Singh (Collaborator), J Wedzicha (Collaborator), A Anzueto (Collaborator), S Braman (Collaborator), R Casaburi (Collaborator), B Celli (Collaborator), G Giessel (Collaborator), M Gotfried (Collaborator), G Greenwald (Collaborator), N Hanania (Collaborator), D Mahler (Collaborator), B Make (Collaborator), S Rennard (Collaborator), C Rochester (Collaborator), P Scanlon (Collaborator), D Schuller (Collaborator), F Sciurba (Collaborator), A Sharafkhaneh (Collaborator), T Siler (Collaborator), E Silverman (Collaborator), R ZuWallack (Collaborator), H Coxson (Collaborator), C Crim (Collaborator), L Edwards (Collaborator), J Yates (Collaborator), B Miller (Collaborator), R Tal-Singer (Collaborator)

Research output: Contribution to journal › Article › peer-review

Abstract

Pulmonary hypertension is associated with advanced chronic obstructive pulmonary disease (COPD), although pulmonary vascular changes occur early in the course of the disease. Pulmonary artery (PA) enlargement (PAE) measured by computed tomography correlates with pulmonary hypertension and COPD exacerbation frequency. Genome-wide association studies of PAE in subjects with COPD have not been reported. To investigate whether genetic variants are associated with PAE within subjects with COPD, we investigated data from current and former smokers from the COPDGene Study and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study. The ratio of the diameter of the PA to the diameter of the aorta (A) was measured using computed tomography. PAE was defined as PA/A greater than 1. A genome-wide association study for COPD with PAE was performed using subjects with COPD without PAE (PA/A ≤ 1) as a control group. A secondary analysis used smokers with normal spirometry as a control group. Genotyping was performed on Illumina platforms. The results were summarized using fixed-effect meta-analysis. Both meta-analyses revealed a genome-wide significant locus on chromosome 15q25.1 in IREB2 (COPD with versus without PAE, rs7181486; odds ratio [OR] = 1.32; P = 2.10 × 10(-8); versus smoking control subjects, rs2009746; OR = 1.42; P = 1.32 × 10(-9)). PAE was also associated with a region on 14q31.3 near the GALC gene (rs7140285; OR = 1.55; P = 3.75 × 10(-8)). Genetic variants near IREB2 and GALC likely contribute to genetic susceptibility to PAE associated with COPD. This study provides evidence for genetic heterogeneity associated with a clinically important COPD vascular subtype.

Original language	English
Journal	American Journal of Respiratory Cell and Molecular Biology
Volume	52
Issue number	3
DOIs	https://doi.org/10.1165/rcmb.2014-0210OC
Publication status	Published - Mar 2015

Keywords

chronic obstructive pulmonary disease
genome-wide association
pulmonary hypertension
subtyping

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1165/rcmb.2014-0210OC

Cite this

Lee, J. H., Wells, J. M., Crapo, J. D., Regan, E. A., Bratschie, S., Lantz, R., Melanson, S., Stepp, L., Beaty, T., Everett, D., Lynch, D., Sutherland, E. R., Bleecker, E. R., Crystal, R. G., Hogg, J. C., Province, M. A., Thomas, D. C., Croxton, T., Gan, W., ... Tal-Singer, R. (2015). IREB2 and GALC are associated with pulmonary artery enlargement in chronic obstructive pulmonary disease. American Journal of Respiratory Cell and Molecular Biology, 52(3). https://doi.org/10.1165/rcmb.2014-0210OC

@article{c4fd5a344b0847f8bd0296cd9a75dadb,

title = "IREB2 and GALC are associated with pulmonary artery enlargement in chronic obstructive pulmonary disease.",

abstract = "Pulmonary hypertension is associated with advanced chronic obstructive pulmonary disease (COPD), although pulmonary vascular changes occur early in the course of the disease. Pulmonary artery (PA) enlargement (PAE) measured by computed tomography correlates with pulmonary hypertension and COPD exacerbation frequency. Genome-wide association studies of PAE in subjects with COPD have not been reported. To investigate whether genetic variants are associated with PAE within subjects with COPD, we investigated data from current and former smokers from the COPDGene Study and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study. The ratio of the diameter of the PA to the diameter of the aorta (A) was measured using computed tomography. PAE was defined as PA/A greater than 1. A genome-wide association study for COPD with PAE was performed using subjects with COPD without PAE (PA/A ≤ 1) as a control group. A secondary analysis used smokers with normal spirometry as a control group. Genotyping was performed on Illumina platforms. The results were summarized using fixed-effect meta-analysis. Both meta-analyses revealed a genome-wide significant locus on chromosome 15q25.1 in IREB2 (COPD with versus without PAE, rs7181486; odds ratio [OR] = 1.32; P = 2.10 × 10(-8); versus smoking control subjects, rs2009746; OR = 1.42; P = 1.32 × 10(-9)). PAE was also associated with a region on 14q31.3 near the GALC gene (rs7140285; OR = 1.55; P = 3.75 × 10(-8)). Genetic variants near IREB2 and GALC likely contribute to genetic susceptibility to PAE associated with COPD. This study provides evidence for genetic heterogeneity associated with a clinically important COPD vascular subtype.",

keywords = "chronic obstructive pulmonary disease, genome-wide association, pulmonary hypertension, subtyping",

author = "Lee, {Jin Hwa} and Wells, {J Michael} and Crapo, {James D} and Regan, {Elizabeth A} and Stephanie Bratschie and Rochelle Lantz and Sandra Melanson and Lori Stepp and Terri Beaty and Douglas Everett and David Lynch and Sutherland, {E Rand} and Bleecker, {Eugene R} and Crystal, {Ronald G} and Hogg, {James C} and Province, {Michael A} and Thomas, {Duncan C} and Thomas Croxton and Weiniu Gan and Lisa Postow and Walsh, {John W} and Delia Prieto and Homayoon Farzadegan and Samantha Bragan and Stacey Cayetano and Daniel Cossette and Kelly, {Roxanne K} and Andre Williams and Ruthie Knowles and Carla Wilson and John Hokanson and Jennifer Black-Shinn and Gregory Kinney and Castaldi, {Peter J} and Michael Cho and Hardin, {Megan E} and Craig Hersh and Jacqueline Hetmanski and Nan Laird and Christoph Lange and Lutz, {Sharon M} and Manuel Mattheisen and Merry-Lynn McDonald and Parker, {Margaret M} and Stephanie Santorico and Wan, {Emily S} and Jin Zhou and {Al Qaisi}, Mustafa and Cox, {Christian W} and Deanna Cusick and Dy, {Jennifer G} and Shoshana Ginsburg and Hoffman, {Eric A} and Judy, {Philip F} and Alex Kluiber and Alexander McKenzie and Newell, {John D} and Reilly, {John J} and James Ross and Estepar, {Raul San Jose} and Jered Sieren and Arkadiusz Sitek and Douglas Stinson and Alejandro Cornellas and Fernando Martinez and Robert Jensen and Jeffrey Curtis and Ella Kazerooni and Alapat, {M Philip} and Venkata Bandi and Kalpalatha Guntupalli and Elizabeth Guy and Antara Mallampalli and Charles Trinh and Mustafa Atik and Hasan Al-Azzawi and Marc Willis and Susan Pinero and Linda Fahr and Arun Nachiappan and Collin Bray and Frigini, {L Alexander} and Carlos Farinas and David Katz and Jose Freytes and AnneMarie Marciel and Dawn DeMeo and George Washko and Francine Jacobson and Hiroto Hatabu and Peter Clarke and Ritu Gill and Andetta Hunsaker and Beatrice Trotman-Dickenson and Rachna Madan and Barr, {R Graham} and Byron Thomashow and John Austin and Belinda D'Souza and Neil MacIntyre and Richard Rosiello and Timothy Bresnahan and Joseph Bradley and Sharon Kuong and Steven Meller and Suzanne Roland and Charlene McEvoy and Joseph Tashjian and Robert Wise and Nadia Hansel and Robert Brown and Gregory Diette and Karen Horton and Janos Porszasz and Hans Fischer and Matt Budoff and Mehdi Rambod and DeBakey, {Michael E} and Hirani Kamal and Roham Darvishi and Dennis Niewoehner and Quentin Anderson and Kathryn Rice and Audrey Caine and Marilyn Foreman and Gloria Westney and Eugene Berkowitz and Russell Bowler and Joyce Schroeder and Valerie Hale and John Armstrong and Debra Dyer and Jonathan Chung and Gerard Criner and Victor Kim and Nathaniel Marchetti and Aditi Satti and Mamary, {A James} and Robert Steiner and Chandra Dass and Libby Cone and William Bailey and Mark Dransfield and Michael Wells and Surya Bhatt and Hrudaya Nath and Satinder Singh and Joe Ramsdell and Paul Friedman and {van Beek}, Edwin and MeiLan Han and Christine Wendt and Tadashi Allen and Joel Weissfeld and Carl Fuhrman and Jessica Bon and Danielle Hooper and Sandra Adams and Carlos Orozco and Mario Ruiz and Amy Mumbower and Ariel Kruger and Carlos Restrepo and Michael Lane and Y Ivanov and K Kostov and J Bourbeau and M Fitzgerald and P Hernandez and K Killian and R Levy and F Maltais and D O'Donnell and J Krepelka and J Vestbo and E Wouters and D Quinn and P Bakke and M Kosnik and A Agusti and J Sauleda and {de Mallorca}, P and Y Feschenko and V Gavrisyuk and L Yashina and N Monogarova and P Calverley and D Lomas and W MacNee and D Singh and J Wedzicha and A Anzueto and S Braman and R Casaburi and B Celli and G Giessel and M Gotfried and G Greenwald and N Hanania and D Mahler and B Make and S Rennard and C Rochester and P Scanlon and D Schuller and F Sciurba and A Sharafkhaneh and T Siler and E Silverman and R ZuWallack and H Coxson and C Crim and L Edwards and J Yates and B Miller and R Tal-Singer",

note = "G0901786, Medical Research Council, United KingdomK08 HL097029, NHLBI NIH HHS, United StatesK08 HL123940, NHLBI NIH HHS, United StatesP01 HL105339, NHLBI NIH HHS, United StatesP01 HL105339, NHLBI NIH HHS, United StatesR01 HL075478, NHLBI NIH HHS, United StatesR01 HL089856, NHLBI NIH HHS, United StatesR01 HL113264, NHLBI NIH HHS, United StatesR01HL089897, NHLBI NIH HHS, United StatesR34 HL109482, NHLBI NIH HHS, United States",

year = "2015",

month = mar,

doi = "10.1165/rcmb.2014-0210OC",

language = "English",

volume = "52",

journal = "American Journal of Respiratory Cell and Molecular Biology",

issn = "1535-4989",

publisher = "American Thoracic Society",

number = "3",

}

Lee, JH, Wells, JM, Crapo, JD, Regan, EA, Bratschie, S, Lantz, R, Melanson, S, Stepp, L, Beaty, T, Everett, D, Lynch, D, Sutherland, ER, Bleecker, ER, Crystal, RG, Hogg, JC, Province, MA, Thomas, DC, Croxton, T, Gan, W, Postow, L, Walsh, JW, Prieto, D, Farzadegan, H, Bragan, S, Cayetano, S, Cossette, D, Kelly, RK, Williams, A, Knowles, R, Wilson, C, Hokanson, J, Black-Shinn, J, Kinney, G, Castaldi, PJ, Cho, M, Hardin, ME, Hersh, C, Hetmanski, J, Laird, N, Lange, C, Lutz, SM, Mattheisen, M, McDonald, M-L, Parker, MM, Santorico, S, Wan, ES, Zhou, J, Al Qaisi, M, Cox, CW, Cusick, D, Dy, JG, Ginsburg, S, Hoffman, EA, Judy, PF, Kluiber, A, McKenzie, A, Newell, JD, Reilly, JJ, Ross, J, Estepar, RSJ, Sieren, J, Sitek, A, Stinson, D, Cornellas, A, Martinez, F, Jensen, R, Curtis, J, Kazerooni, E, Alapat, MP, Bandi, V, Guntupalli, K, Guy, E, Mallampalli, A, Trinh, C, Atik, M, Al-Azzawi, H, Willis, M, Pinero, S, Fahr, L, Nachiappan, A, Bray, C, Frigini, LA, Farinas, C, Katz, D, Freytes, J, Marciel, A, DeMeo, D, Washko, G, Jacobson, F, Hatabu, H, Clarke, P, Gill, R, Hunsaker, A, Trotman-Dickenson, B, Madan, R, Barr, RG, Thomashow, B, Austin, J, D'Souza, B, MacIntyre, N, Rosiello, R, Bresnahan, T, Bradley, J, Kuong, S, Meller, S, Roland, S, McEvoy, C, Tashjian, J, Wise, R, Hansel, N, Brown, R, Diette, G, Horton, K, Porszasz, J, Fischer, H, Budoff, M, Rambod, M, DeBakey, ME, Kamal, H, Darvishi, R, Niewoehner, D, Anderson, Q, Rice, K, Caine, A, Foreman, M, Westney, G, Berkowitz, E, Bowler, R, Schroeder, J, Hale, V, Armstrong, J, Dyer, D, Chung, J, Criner, G, Kim, V, Marchetti, N, Satti, A, Mamary, AJ, Steiner, R, Dass, C, Cone, L, Bailey, W, Dransfield, M, Wells, M, Bhatt, S, Nath, H, Singh, S, Ramsdell, J, Friedman, P, van Beek, E, Han, M, Wendt, C, Allen, T, Weissfeld, J, Fuhrman, C, Bon, J, Hooper, D, Adams, S, Orozco, C, Ruiz, M, Mumbower, A, Kruger, A, Restrepo, C, Lane, M, Ivanov, Y, Kostov, K, Bourbeau, J, Fitzgerald, M, Hernandez, P, Killian, K, Levy, R, Maltais, F, O'Donnell, D, Krepelka, J, Vestbo, J, Wouters, E, Quinn, D, Bakke, P, Kosnik, M, Agusti, A, Sauleda, J, de Mallorca, P, Feschenko, Y, Gavrisyuk, V, Yashina, L, Monogarova, N, Calverley, P, Lomas, D, MacNee, W, Singh, D, Wedzicha, J, Anzueto, A, Braman, S, Casaburi, R, Celli, B, Giessel, G, Gotfried, M, Greenwald, G, Hanania, N, Mahler, D, Make, B, Rennard, S, Rochester, C, Scanlon, P, Schuller, D, Sciurba, F, Sharafkhaneh, A, Siler, T, Silverman, E, ZuWallack, R, Coxson, H, Crim, C, Edwards, L, Yates, J, Miller, B & Tal-Singer, R 2015, 'IREB2 and GALC are associated with pulmonary artery enlargement in chronic obstructive pulmonary disease.', American Journal of Respiratory Cell and Molecular Biology, vol. 52, no. 3. https://doi.org/10.1165/rcmb.2014-0210OC

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AU - Lee, Jin Hwa

AU - Wells, J Michael

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A2 - Wilson, Carla

A2 - Hokanson, John

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A2 - Castaldi, Peter J

A2 - Cho, Michael

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A2 - Mattheisen, Manuel

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A2 - Santorico, Stephanie

A2 - Wan, Emily S

A2 - Zhou, Jin

A2 - Al Qaisi, Mustafa

A2 - Cox, Christian W

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A2 - Hoffman, Eric A

A2 - Judy, Philip F

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A2 - McKenzie, Alexander

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A2 - Estepar, Raul San Jose

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A2 - Martinez, Fernando

A2 - Jensen, Robert

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A2 - Kazerooni, Ella

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A2 - Bandi, Venkata

A2 - Guntupalli, Kalpalatha

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A2 - Mallampalli, Antara

A2 - Trinh, Charles

A2 - Atik, Mustafa

A2 - Al-Azzawi, Hasan

A2 - Willis, Marc

A2 - Pinero, Susan

A2 - Fahr, Linda

A2 - Nachiappan, Arun

A2 - Bray, Collin

A2 - Frigini, L Alexander

A2 - Farinas, Carlos

A2 - Katz, David

A2 - Freytes, Jose

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A2 - Washko, George

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A2 - Clarke, Peter

A2 - Gill, Ritu

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A2 - Thomashow, Byron

A2 - Austin, John

A2 - D'Souza, Belinda

A2 - MacIntyre, Neil

A2 - Rosiello, Richard

A2 - Bresnahan, Timothy

A2 - Bradley, Joseph

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A2 - Meller, Steven

A2 - Roland, Suzanne

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A2 - Tashjian, Joseph

A2 - Wise, Robert

A2 - Hansel, Nadia

A2 - Brown, Robert

A2 - Diette, Gregory

A2 - Horton, Karen

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A2 - Fischer, Hans

A2 - Budoff, Matt

A2 - Rambod, Mehdi

A2 - DeBakey, Michael E

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A2 - Niewoehner, Dennis

A2 - Anderson, Quentin

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A2 - Caine, Audrey

A2 - Foreman, Marilyn

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A2 - Dyer, Debra

A2 - Chung, Jonathan

A2 - Criner, Gerard

A2 - Kim, Victor

A2 - Marchetti, Nathaniel

A2 - Satti, Aditi

A2 - Mamary, A James

A2 - Steiner, Robert

A2 - Dass, Chandra

A2 - Cone, Libby

A2 - Bailey, William

A2 - Dransfield, Mark

A2 - Wells, Michael

A2 - Bhatt, Surya

A2 - Nath, Hrudaya

A2 - Singh, Satinder

A2 - Ramsdell, Joe

A2 - Friedman, Paul

A2 - van Beek, Edwin

A2 - Han, MeiLan

A2 - Wendt, Christine

A2 - Allen, Tadashi

A2 - Weissfeld, Joel

A2 - Fuhrman, Carl

A2 - Bon, Jessica

A2 - Hooper, Danielle

A2 - Adams, Sandra

A2 - Orozco, Carlos

A2 - Ruiz, Mario

A2 - Mumbower, Amy

A2 - Kruger, Ariel

A2 - Restrepo, Carlos

A2 - Lane, Michael

A2 - Ivanov, Y

A2 - Kostov, K

A2 - Bourbeau, J

A2 - Fitzgerald, M

A2 - Hernandez, P

A2 - Killian, K

A2 - Levy, R

A2 - Maltais, F

A2 - O'Donnell, D

A2 - Krepelka, J

A2 - Vestbo, J

A2 - Wouters, E

A2 - Quinn, D

A2 - Bakke, P

A2 - Kosnik, M

A2 - Agusti, A

A2 - Sauleda, J

A2 - de Mallorca, P

A2 - Feschenko, Y

A2 - Gavrisyuk, V

A2 - Yashina, L

A2 - Monogarova, N

A2 - Calverley, P

A2 - Lomas, D

A2 - MacNee, W

A2 - Singh, D

A2 - Wedzicha, J

A2 - Anzueto, A

A2 - Braman, S

A2 - Casaburi, R

A2 - Celli, B

A2 - Giessel, G

A2 - Gotfried, M

A2 - Greenwald, G

A2 - Hanania, N

A2 - Mahler, D

A2 - Make, B

A2 - Rennard, S

A2 - Rochester, C

A2 - Scanlon, P

A2 - Schuller, D

A2 - Sciurba, F

A2 - Sharafkhaneh, A

A2 - Siler, T

A2 - Silverman, E

A2 - ZuWallack, R

A2 - Coxson, H

A2 - Crim, C

A2 - Edwards, L

A2 - Yates, J

A2 - Miller, B

A2 - Tal-Singer, R

N1 - G0901786, Medical Research Council, United KingdomK08 HL097029, NHLBI NIH HHS, United StatesK08 HL123940, NHLBI NIH HHS, United StatesP01 HL105339, NHLBI NIH HHS, United StatesP01 HL105339, NHLBI NIH HHS, United StatesR01 HL075478, NHLBI NIH HHS, United StatesR01 HL089856, NHLBI NIH HHS, United StatesR01 HL113264, NHLBI NIH HHS, United StatesR01HL089897, NHLBI NIH HHS, United StatesR34 HL109482, NHLBI NIH HHS, United States

PY - 2015/3

Y1 - 2015/3

N2 - Pulmonary hypertension is associated with advanced chronic obstructive pulmonary disease (COPD), although pulmonary vascular changes occur early in the course of the disease. Pulmonary artery (PA) enlargement (PAE) measured by computed tomography correlates with pulmonary hypertension and COPD exacerbation frequency. Genome-wide association studies of PAE in subjects with COPD have not been reported. To investigate whether genetic variants are associated with PAE within subjects with COPD, we investigated data from current and former smokers from the COPDGene Study and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study. The ratio of the diameter of the PA to the diameter of the aorta (A) was measured using computed tomography. PAE was defined as PA/A greater than 1. A genome-wide association study for COPD with PAE was performed using subjects with COPD without PAE (PA/A ≤ 1) as a control group. A secondary analysis used smokers with normal spirometry as a control group. Genotyping was performed on Illumina platforms. The results were summarized using fixed-effect meta-analysis. Both meta-analyses revealed a genome-wide significant locus on chromosome 15q25.1 in IREB2 (COPD with versus without PAE, rs7181486; odds ratio [OR] = 1.32; P = 2.10 × 10(-8); versus smoking control subjects, rs2009746; OR = 1.42; P = 1.32 × 10(-9)). PAE was also associated with a region on 14q31.3 near the GALC gene (rs7140285; OR = 1.55; P = 3.75 × 10(-8)). Genetic variants near IREB2 and GALC likely contribute to genetic susceptibility to PAE associated with COPD. This study provides evidence for genetic heterogeneity associated with a clinically important COPD vascular subtype.

AB - Pulmonary hypertension is associated with advanced chronic obstructive pulmonary disease (COPD), although pulmonary vascular changes occur early in the course of the disease. Pulmonary artery (PA) enlargement (PAE) measured by computed tomography correlates with pulmonary hypertension and COPD exacerbation frequency. Genome-wide association studies of PAE in subjects with COPD have not been reported. To investigate whether genetic variants are associated with PAE within subjects with COPD, we investigated data from current and former smokers from the COPDGene Study and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study. The ratio of the diameter of the PA to the diameter of the aorta (A) was measured using computed tomography. PAE was defined as PA/A greater than 1. A genome-wide association study for COPD with PAE was performed using subjects with COPD without PAE (PA/A ≤ 1) as a control group. A secondary analysis used smokers with normal spirometry as a control group. Genotyping was performed on Illumina platforms. The results were summarized using fixed-effect meta-analysis. Both meta-analyses revealed a genome-wide significant locus on chromosome 15q25.1 in IREB2 (COPD with versus without PAE, rs7181486; odds ratio [OR] = 1.32; P = 2.10 × 10(-8); versus smoking control subjects, rs2009746; OR = 1.42; P = 1.32 × 10(-9)). PAE was also associated with a region on 14q31.3 near the GALC gene (rs7140285; OR = 1.55; P = 3.75 × 10(-8)). Genetic variants near IREB2 and GALC likely contribute to genetic susceptibility to PAE associated with COPD. This study provides evidence for genetic heterogeneity associated with a clinically important COPD vascular subtype.

KW - chronic obstructive pulmonary disease

KW - genome-wide association

KW - pulmonary hypertension

KW - subtyping

U2 - 10.1165/rcmb.2014-0210OC

DO - 10.1165/rcmb.2014-0210OC

M3 - Article

C2 - 25101718

SN - 1535-4989

VL - 52

JO - American Journal of Respiratory Cell and Molecular Biology

JF - American Journal of Respiratory Cell and Molecular Biology

IS - 3

ER -

IREB2 and GALC are associated with pulmonary artery enlargement in chronic obstructive pulmonary disease.

Abstract

Keywords

UN SDGs

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